tbuckley/cabot-search huggingface dataset:
The gut microbiome in Alzheimer’s disease: what we know and what remains to be explored
Authors: Sidhanth Chandra, Sangram S. Sisodia, Robert J. Vassar
Journal: Molecular Neurodegeneration (2023)

Alzheimer's disease (AD), the most common cause of dementia, results in a sustained decline in cognition. There are currently few effective disease modifying therapies for AD, but insights into the mechanisms that mediate the onset and progression of disease may lead to new, effective therapeutic strategies. Amyloid beta oligomers and plaques, tau aggregates, and neuroinflammation play a critical role in neurodegeneration and impact clinical AD progression. The upstream modulators of these pathological features have not been fully clarified, but recent evidence indicates that the gut microbiome (GMB) may have an influence on these features and therefore may influence AD progression in human patients. In this review, we summarize studies that have identified alterations in the GMB that correlate with pathophysiology in AD patients and AD mouse models. Additionally, we discuss findings with GMB manipulations in AD models and potential GMB-targeted therapeutics for AD. Lastly, we discuss diet, sleep, and exercise as potential modifiers of the relationship between the GMB and AD and conclude with future directions and recommendations for further studies of this topic.
Author correction to “The FAPα-activated prodrug Z-GP-DAVLBH inhibits the growth and pulmonary metastasis of osteosarcoma cells by suppressing the AXL pathway” [Acta Pharm Sin B 12 (2022) 1288–1304]
Authors: Geni Ye, Maohua Huang, Yong Li, Jie Ouyang, Minfeng Chen, Qing Weng, Xiaobo Li, Huhu Zeng, Pei Long, Zepei Fan, Junqiang Yin, Wencai Ye, Dongmei Zhang
Journal: Acta Pharmaceutica Sinica B (2023)

[This corrects the article DOI: 10.1016/j.apsb.2021.08.015.].
Potential health benefits of integrated screening strategies for alcohol, tobacco, other substance use, depression, anxiety, and chronic pain among people living with HIV in the USA: a mathematical modelling study
Authors: Anna Bershteyn, Emma Richard, Qinlian Zhou, Maria R Khan, Joy D Scheidell, Prima Manandhar-Sasaki, Kaoon Ban, Stephen Crystal, Adam J Gordon, Amy C Justice, Kendall J Bryant, R Scott Braithwaite
Journal: The Lancet HIV (2023)
Association of society of dermatology hospitalist institutions with improved outcomes in Medicare beneficiaries hospitalized for skin disease
Authors: Pranav Puri, Benjamin D. Pollock, Miranda Yousif, Puneet K. Bhullar, Blake W. Boudreaux, Lindy P. Fox, Misha Rosenbach, Mark R. Pittelkow, Aaron R. Mangold
Journal: Journal of the American Academy of Dermatology (2023)
Enhanced transmissibility, infectivity, and immune resistance of the SARS-CoV-2 omicron XBB.1.5 variant
Authors: Keiya Uriu, Jumpei Ito, Jiri Zahradnik, Shigeru Fujita, Yusuke Kosugi, Gideon Schreiber, Kei Sato
Journal: The Lancet Infectious Diseases (2023)
Cooling cities through urban green infrastructure: a health impact assessment of European cities
Authors: Tamara Iungman, Marta Cirach, Federica Marando, Evelise Pereira Barboza, Sasha Khomenko, Pierre Masselot, Marcos Quijal-Zamorano, Natalie Mueller, Antonio Gasparrini, José Urquiza, Mehdi Heris, Meelan Thondoo, Mark Nieuwenhuijsen
Journal: The Lancet (2023)
A novel strategy to perform endoscopic full-thickness resection at the ileocecal valve and securing the orifice with a double-pigtail catheter
Authors: Moritz Meiborg, Nicolae-Catalin Mechie, Tobias Blasberg, Marie Weber, Edris Wedi
Journal: Endoscopy (2023)

A 68-year-old woman was referred to our clinic for evaluation of endoscopic resection of a flat polyp on the ileocecal valve.
Introducer-assisted endoscopic transpapillary gallbladder biopsy for indeterminate gallbladder fundal wall thickness
Authors: Tesshin Ban, Kazuki Hayashi, Yoshimasa Kubota, Makoto Urano, Takuya Takahama, Yoichi Matsuo, Takashi Joh
Journal: Endoscopy (2023)

Endoscopic transpapillary gallbladder biopsy (ET-GBBx) remains challenging; therefore, there is no recommendation for the histological examination of patients with resectable gallbladder cancer [1] [2]. Endoscopic introducer-assisted procedures recently emerged for pancreatico-biliary interventions [3]. This article describes the use of introducer-assisted ET-GBBx for indeterminate gallbladder fundal wall thickening.
Incorporating genetics in identifying peanut allergy risk and tailoring allergen immunotherapy: A perspective on the genetic findings from the LEAP trial
Authors: Michelle F. Huffaker, Kanika Kanchan, Henry T. Bahnson, Carolyn Baloh, Gideon Lack, Gerald T. Nepom, Rasika A. Mathias
Journal: Journal of Allergy and Clinical Immunology (2023)
Endoscopic ultrasound-guided transduodenal drainage using forward-viewing echoendoscope for appendiceal abscess
Authors: Kazuya Koizumi, Sakue Masuda, Makomo Makazu, Haruto Hirose, Ryuhei Jinushi, Kento Shionoya, Yuma Suno
Journal: Endoscopy (2023)

Appendiceal abscesses sometimes require percutaneous drainage [1]. Recently, endoscopic ultrasound (EUS)-guided drainage through the intestinal tract has become possible, even in cases of pelvic or intra-abdominal abscesses resulting from lower gastrointestinal tract disease. However, this approach is usually performed through the rectum or sigmoid colon [2] [3] [4] [5], and its use is challenging for appendiceal abscesses because of their location. Herein, we report a case of appendiceal abscess successfully treated by EUS-guided transduodenal drainage using a forward-viewing echoendoscope.
Endoscopic ultrasound-guided rendezvous technique in a transduodenal long endoscopic position using a 22 G needle combined with a novel 0.018-inch guidewire
Authors: Shogo Ota, Hideyuki Shiomi, Ryota Nakano, Hiroko Iijima
Journal: Endoscopy (2023)

The endoscopic ultrasound-guided rendezvous technique (EUS-RV) is a salvage technique for failed biliary cannulation with benign disorders, but its success rate is not high [1] [2] [3]. The approach in a transduodenal, long endoscopic position (TDL) is preferred because it provides easier access to the bile duct, even if the bile duct is not dilated, as it stabilizes the scope position [4]. However, the TDL method, with a combination of a 19 G needle and 0.025-inch guidewire, directs the puncture needle toward the hepatic hilum because the range of motion of the scope and the needle is limited, making guidewire advance to the papilla challenging. Recently, a novel 0.018-inch guidewire (Fielder 18; Olympus, Tokyo, Japan) has been developed, which is similar to a 0.025-inch guidewire with good visibility, maneuverability, and stiffness ([Fig. 1]). Compared with the 19 G needle with 0.025-inch guidewire, a 22 G needle with the 0.018-inch guidewire has a more extensive range of motion for puncture, and the scope can be bent more acutely ([Fig. 2], [Fig. 3]). Therefore, the tip of the puncture needle can be directed toward the papilla, and the excellent maneuverability of this guidewire allows easier advance into the duodenum ([Fig. 4]). The 22 G needle may prevent bile leakage during the procedure due to its smaller diameter.
Handbook of Refugee Health: a timely guide to effective provision of refugee health services
Authors: Neema Kaseje, Francine Bazompora Munezero
Journal: BMJ (2023)

Almost eight million people including many children have fled Ukraine seeking safety, protection, and assistance since the Russian invasion. 1There is renewed violence in the eastern part of the Democratic Republic of the Congo, with the displacement of thousands of women and children. 2 Globally, there are more than 100 million displaced populations fleeing conflict, violence, or persecution. 3 4During their migration journeys, refugees, particularly women and children, face high risks of violence, including sexual violence.
Alligator forceps-assisted piecemeal endoscopic mucosal resection for a large laterally spreading tumor of the papilla
Authors: Xi Zheng, Fei Ao, Huan He, Weiqing Chen
Journal: Endoscopy (2023)

A 54-year-old woman was referred to our hospital for an incidentally found 26-mm laterally spreading tumor of the papilla (LST-P) ([Fig. 1]). Magnifying endoscopy with narrow-band imaging showed irregular pits with a dilated subepithelial capillary network. A biopsy showed the polyp to be a tubular adenoma. Endoscopic ultrasound (EUS) revealed that this adenoma was limited to the mucosa and had no intraductal extension into the pancreatic duct or the common bile duct ([Fig. 2]). Endoscopic mucosal resection (EMR) of large (10–29 mm) LST-P carries a risk of delayed bleeding and perforation [1]. In terms of shortening the operation time and reducing the perforation, we innovatively use alligator forceps to achieve sufficient traction for duodenal piecemeal endoscopic mucosal resection (pEMR).
Growing Income-Related Disparities in Cardiovascular Hospitalizations Among People With Diabetes, 1995–2019: A Population-Based Study
Authors: Baiju R. Shah, Peter C. Austin, Calvin Ke, Lorraine L. Lipscombe, Alanna Weisman, Gillian L. Booth
Journal: Diabetes Care (2023)

OBJECTIVE Cardiovascular risk reduction is an important focus in the management of people with diabetes. Although event rates have been declining over the long term, they have been observed to plateau or reverse in recent years. Furthermore, the impact of income-related disparities in cardiovascular events is unknown. The objective of this study is to evaluate age-, sex-, and income-related trends in cardiovascular hospitalization rates among people with diagnosed diabetes. RESEARCH DESIGN AND METHODS We calculated rates of hospitalization for acute myocardial infarction, stroke, heart failure, and lower-extremity amputation in annual cohorts of the entire population of Ontario, Canada, with diagnosed diabetes, from 1995 to 2019. Event rates were stratified by age, sex, and income level. RESULTS We studied nearly 1.7 million people with diabetes. The rate of acute myocardial infarction declined throughout the 25-year study period (P &amp;lt; 0.0001), such that the rate in 2019 was less than half the rate in 1995. Rates of stroke (P &amp;lt; 0.0001), heart failure (P &amp;lt; 0.0001), and amputation (P &amp;lt; 0.0001) also changed over time, but hospitalization rates stabilized through the 2010s. This apparent stabilization concealed a growing income-related disparity: wealthier patients showed continued declines in rates of these outcomes during the decade, whereas rates for lower-income patients increased (P for interaction &amp;lt; 0.0001 for all four outcomes). CONCLUSIONS During a quarter-century of follow-up, cardiovascular hospitalization rates among people with diabetes fell. However, the apparent stabilization in rates of stroke, heart failure, and amputation in recent years masks the fact that rates have risen for lower-income individuals.
Activity of eftozanermin alfa plus venetoclax in preclinical models and patients with acute myeloid leukemia
Authors: Stephen K. Tahir, Emiliano Calvo, Benedito A. Carneiro, Junichiro Yuda, Aditya Shreenivas, Mojca Jongen-Lavrencic, Eelke Gort, Kenichi Ishizawa, Daniel Morillo, Carla Biesdorf, Morey Smith, Dong Cheng, Monica Motwani, David Sharon, Tamar Uziel, Dimple A. Modi, Fritz G. Buchanan, Susan Morgan-Lappe, Bruno C. Medeiros, Darren C. Phillips
Journal: Blood (2023)

Abstract Activation of apoptosis in malignant cells is an established strategy for controlling cancer and is potentially curative. To assess the impact of concurrently inducing the extrinsic and intrinsic apoptosis-signaling pathways in acute myeloid leukemia (AML), we evaluated activity of the TRAIL receptor agonistic fusion protein eftozanermin alfa (eftoza; ABBV-621) in combination with the B-cell lymphoma protein-2 selective inhibitor venetoclax in preclinical models and human patients. Simultaneously stimulating intrinsic and extrinsic apoptosis-signaling pathways with venetoclax and eftoza, respectively, enhanced their activities in AML cell lines and patient-derived ex vivo/in vivo models. Eftoza activity alone or plus venetoclax required death receptor 4/5 (DR4/DR5) expression on the plasma membrane but was independent of TP53 or FLT3-ITD status. The safety/tolerability of eftoza as monotherapy and in combination with venetoclax was demonstrated in patients with relapsed/refractory AML in a phase 1 clinical trial. Treatment-related adverse events were reported in 2 of 4 (50%) patients treated with eftoza monotherapy and 18 of 23 (78%) treated with eftoza plus venetoclax. An overall response rate of 30% (7/23; 4 complete responses [CRs], 2 CRs with incomplete hematologic recovery, and 1 morphologic leukemia-free state) was reported in patients who received treatment with eftoza plus venetoclax and 67% (4/6) in patients with myoblasts positive for DR4/DR5 expression; no tumor responses were observed with eftoza monotherapy. These data indicate that combination therapy with eftoza plus venetoclax to simultaneously activate the extrinsic and intrinsic apoptosis-signaling pathways may improve clinical benefit compared with venetoclax monotherapy in relapsed/refractory AML with an acceptable toxicity profile. This trial was registered at www.clinicaltrials.gov as #NCT03082209.
Validation of the Molecular International Prognostic Scoring System in patients with myelodysplastic syndromes
Authors: Tariq Kewan, Waled Bahaj, Arda Durmaz, Mai Aly, Olisaemeka D. Ogbue, Hetty E. Carraway, Mikkael A. Sekeres, Valeria Visconte, Carmelo Gurnari, Jaroslaw P. Maciejewski
Journal: Blood (2023)
CD73-Dependent Adenosine Signaling through Adora2b Drives Immunosuppression in Ductal Pancreatic Cancer
Authors: Erika Y. Faraoni, Kanchan Singh, Vidhi Chandra, Olivereen Le Roux, Yulin Dai, Ismet Sahin, Baylee J. O'Brien, Lincoln N. Strickland, Le Li, Emily Vucic, Amanda N. Warner, Melissa Pruski, Trent Clark, George Van Buren, Nirav C. Thosani, John S. Bynon, Curtis J. Wray, Dafna Bar-Sagi, Kyle L. Poulsen, Lana A. Vornik, Michelle I. Savage, Shizuko Sei, Altaf Mohammed, Zhongming Zhao, Powel H. Brown, Tingting Mills, Holger K. Eltzschig, Florencia McAllister, Jennifer M. Bailey-Lundberg
Journal: Cancer Research (2023)

Abstract The microenvironment that surrounds pancreatic ductal adenocarcinoma (PDAC) is profoundly desmoplastic and immunosuppressive. Understanding triggers of immunosuppression during the process of pancreatic tumorigenesis would aid in establishing targets for effective prevention and therapy. Here, we interrogated differential molecular mechanisms dependent on cell of origin and subtype that promote immunosuppression during PDAC initiation and in established tumors. Transcriptomic analysis of cell-of-origin–dependent epithelial gene signatures revealed that Nt5e/CD73, a cell-surface enzyme required for extracellular adenosine generation, is one of the top 10% of genes overexpressed in murine tumors arising from the ductal pancreatic epithelium as opposed to those rising from acinar cells. These findings were confirmed by IHC and high-performance liquid chromatography. Analysis in human PDAC subtypes indicated that high Nt5e in murine ductal PDAC models overlaps with high NT5E in human PDAC squamous and basal subtypes, considered to have the highest immunosuppression and worst prognosis. Multiplex immunofluorescent analysis showed that activated CD8+ T cells in the PDAC tumor microenvironment express high levels of CD73, indicating an opportunity for immunotherapeutic targeting. Delivery of CD73 small-molecule inhibitors through various delivery routes reduced tumor development and growth in genetically engineered and syngeneic mouse models. In addition, the adenosine receptor Adora2b was a determinant of adenosine-mediated immunosuppression in PDAC. These findings highlight a molecular trigger of the immunosuppressive PDAC microenvironment elevated in the ductal cell of origin, linking biology with subtype classification, critical components for PDAC immunoprevention and personalized approaches for immunotherapeutic intervention. Significance: Ductal-derived pancreatic tumors have elevated epithelial and CD8+GZM+ T-cell CD73 expression that confers sensitivity to small-molecule inhibition of CD73 or Adora2b to promote CD8+ T-cell–mediated tumor regression. See related commentary by DelGiorno, p. 977
Adjuvant Osimertinib for Resected EGFR-Mutated Stage IB-IIIA Non–Small-Cell Lung Cancer: Updated Results From the Phase III Randomized ADAURA Trial
Authors: Roy S. Herbst, Yi-Long Wu, Thomas John, Christian Grohe, Margarita Majem, Jie Wang, Terufumi Kato, Jonathan W. Goldman, Konstantin Laktionov, Sang-We Kim, Chong-Jen Yu, Huu Vinh Vu, Shun Lu, Kye Young Lee, Guzel Mukhametshina, Charuwan Akewanlop, Filippo de Marinis, Laura Bonanno, Manuel Domine, Frances A. Shepherd, Damien Urban, Xiangning Huang, Ana Bolanos, Marta Stachowiak, Masahiro Tsuboi
Journal: Journal of Clinical Oncology (2023)

The phase III ADAURA (ClinicalTrials.gov identifier: NCT02511106) primary analysis demonstrated a clinically significant disease-free survival (DFS) benefit with adjuvant osimertinib versus placebo in EGFR-mutated stage IB-IIIA non-small-cell lung cancer (NSCLC) after complete tumor resection (DFS hazard ratio [HR], 0.20 [99.12% CI, 0.14 to 0.30];
Real-world effectiveness of a single dose of mpox vaccine in males
Authors: Yael Wolff Sagy, Roy Zucker, Ariel Hammerman, Hila Markovits, Noa Gur Arieh, Wiessam Abu Ahmad, Erez Battat, Noga Ramot, Guy Carmeli, Avner Mark-Amir, Gal Wagner-Kolasko, Hadar Duskin-Bitan, Shlomit Yaron, Alon Peretz, Ronen Arbel, Gil Lavie, Doron Netzer
Journal: Nature Medicine (2023)
Microbial transmission, colonisation and succession: from pregnancy to infancy
Authors: Liwen Xiao, Fangqing Zhao
Journal: Gut (2023)

The microbiome has been proven to be associated with many diseases and has been used as a biomarker and target in disease prevention and intervention. Currently, the vital role of the microbiome in pregnant women and newborns is increasingly emphasised. In this review, we discuss the interplay of the microbiome and the corresponding immune mechanism between mothers and their offspring during the perinatal period. We aim to present a comprehensive picture of microbial transmission and potential immune imprinting before and after delivery. In addition, we discuss the possibility of in utero microbial colonisation during pregnancy, which has been highly debated in recent studies, and highlight the importance of the microbiome in infant development during the first 3 years of life. This holistic view of the role of the microbial interplay between mothers and infants will refine our current understanding of pregnancy complications as well as diseases in early life and will greatly facilitate the microbiome-based prenatal diagnosis and treatment of mother-infant-related diseases.
Impact of cardiovascular risk enrichment on incidence of major adverse cardiovascular events in the tofacitinib rheumatoid arthritis clinical programme
Authors: Maxime Dougados, Christina Charles-Schoeman, Zoltán Szekanecz, Jon T Giles, Steven R Ytterberg, Deepak L Bhatt, Gary G Koch, Ivana Vranic, Joseph Wu, Cunshan Wang, Kenneth Kwok, Sujatha Menon, Carol A Connell, Arne Yndestad, Jose L Rivas, Maya H Buch
Journal: Annals of the Rheumatic Diseases (2023)

A recent report from the Belimumab Pregnancy Registry (NCT01532310) analysed available data on the consequences of belimumab (BEL) use in pregnant women with systemic lupus erythematosus (SLE). 1 Although limited by multiple confounders and methodological differences, the study did not reveal an on July 21,
Author Correction: Within-job gender pay inequality in 15 countries
Authors: Andrew M. Penner, Trond Petersen, Are Skeie Hermansen, Anthony Rainey, István Boza, Marta M. Elvira, Olivier Godechot, Martin Hällsten, Lasse Folke Henriksen, Feng Hou, Aleksandra Kanjuo Mrčela, Joe King, Naomi Kodama, Tali Kristal, Alena Křížková, Zoltán Lippényi, Silvia Maja Melzer, Eunmi Mun, Paula Apascaritei, Dustin Avent-Holt, Nina Bandelj, Gergely Hajdu, Jiwook Jung, Andreja Poje, Halil Sabanci, Mirna Safi, Matthew Soener, Donald Tomaskovic-Devey, Zaibu Tufail
Journal: Nature Human Behaviour (2023)
Combined therapy of prednisone and mTOR inhibitor sirolimus for treating retroperitoneal fibrosis
Authors: Hui Gao, Shibo Liu, Yuanbang Mai, Yuying Wang, Xuewu Zhang, Shufen Zheng, Chenghua Luo, Cuiping Pan
Journal: Annals of the Rheumatic Diseases (2023)

Retroperitoneal fibrosis (RPF) is a rare autoimmune disease with fibrous tissue growth and inflammation in retroperitoneum. Its current treatments involve long-term uptake of glucocorticoids (e.g., prednisone) for controlling inflammation; however, side effects are common. We strived for an improved therapy for fibrosis remission while reducing side effects.We surveyed gene-disease-drug databases and discovered that mammalian target of rapamycin (mTOR) was a key signalling protein in RPF and the mTOR inhibitor compound sirolimus affected many RPF pathways. We designed a therapy combining a gradual reduction of prednisone with a long-term, stable dosage of sirolimus. We then implemented a single-arm clinical trial and assessed the effects in eight RPF patients at 0, 12 and 48 weeks of treatment by measuring fibrous tissue mass by CT, markers of inflammation and kidney functions by lab tests, immune cell profiles by flow cytometry and plasma inflammatory proteins by Olink proteomics.With the combined therapy, fibrous tissue shrunk about by half, markers of acute inflammation reduced by 70% and most patients with abnormal kidney functions had them restored to normal range. Molecularly, fibrosis-related T cell subsets, including TH2, TH17 and circulating TFH cells, were reduced and tumour necrosis factor and related cytokines restored to healthy levels. No severe long-term side effects were observed.Our combined therapy resulted in significant fibrosis remission and an overall regression of the immune system towards healthy states, while achieving good tolerance. We concluded that this new therapy had the potential to replace the steroid monotherapy for treating RPF.
Persistence of seroconversion at 6 months following primary immunisation in patients with immune-mediated inflammatory diseases
Authors: Luuk Wieske, Eileen W Stalman, P J Koos van Dam, Laura Y Kummer, Maurice Steenhuis, Zoe L E van Kempen, Joep Killestein, Adriaan G Volkers, Sander W Tas, Laura Boekel, Gertjan Wolbink, Anneke Van der Kooi, Joost Raaphorst, Mark Löwenberg, Bart Takkenberg, Geert R A M D’Haens, Phyllis I Spuls, Marcel W Bekkenk, Annelie H Musters, Nicoline F Post, Angela L Bosma, Marc L Hilhorst, Yosta Vegting, Frederique J Bemelman, Alexandre Voskuyl, Bo Broens, Agner Parra Sanchez, Cécile A C M van Els, Jelle De Wit, Abraham Rutgers, Karina de Leeuw, Barbara Horváth, Jan J G M Verschuuren, Annabel M Ruiter, Lotte van Ouwerkerk, Diane van der Woude, Cornelia F Allaart, Y K Onno Teng, Pieter van Paassen, Matthias H Busch, Papay B P Jallah, Esther Brusse, Pieter A van Doorn, Adája Elisabeth Baars, Dirkjan Hijnen, Corine R G Schreurs, W Ludo Van der Pol, H Stephan Goedee, Sofie Keijzer, Jim Keijser, Olvi Cristianawati, Anja ten Brinke, Niels J M Verstegen, Koos A H Zwinderman, S Marieke van Ham, Taco W Kuijpers, Theo Rispens, Filip Eftimov
Journal: Annals of the Rheumatic Diseases (2023)

The sponsor had no role in the design, analyses or reporting of the study.Competing interests FE and TWK report (governmental) grants from ZonMw to studyimmune response after SARS-Cov-2 vaccination in autoimmune diseases.